Human Papillomavirus and Related Diseases Report MEXICO

Human Papillomavirus and Related Diseases Report MEXICO Version posted at www.hpvcentre.net on 10 December 2018

- ii - Copyright and Permissions ICO/IARC Information Centre on HPV and Cancer (HPV Information Centre) 2018 All rights reserved. HPV Information Centre publications can be obtained from the HPV Information Centre Secretariat, Institut Català d Oncologia, Avda. Gran Via de l Hospitalet, 199-203 08908 L Hospitalet del Llobregat (Barcelona) Spain. E-mail: hpvcentre@iconcologia.net. Requests for permission to reproduce or translate HPV Information Centre publications - whether for sale or for noncommercial distribution- should be addressed to the HPV Information Centre Secretariat, at the above address. The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part the HPV Information Centre concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers products does not imply that they are endorsed or recommended the HPV Information Centre in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. All reasonable precautions have been taken by the HPV Information Centre to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either expressed or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall the HPV Information Centre be liable for damages arising from its use. The development of this report has been supported by grants from the European Comission (7th Framework Programme grant HEALTH-F3-2010-242061, HEALTH-F2-2011-282562, HPV AHEAD). Recommended citation: Bruni L, Albero G, Serrano B, Mena M, Gómez D, Muñoz J, Bosch FX, de Sanjosé S. ICO/IARC Information Centre on HPV and Cancer (HPV Information Centre). Human Papillomavirus and Related Diseases in Mexico. Summary Report 10 December 2018. [Date Accessed]

- iii - Executive summary Human papillomavirus (HPV) infection is now a well-established cause of cervical cancer and there is growing evidence of HPV being a relevant factor in other anogenital cancers (anus, vulva, vagina and penis) as well as head and neck cancers. HPV types 16 and 18 are responsible for about 70% of all cervical cancer cases worldwide. HPV vaccines that prevent HPV 16 and 18 infections are now available and have the potential to reduce the incidence of cervical and other anogenital cancers. This report provides key information for Mexico on: cervical cancer; other anogenital cancers and head and neck cancers; HPV-related statistics; factors contributing to cervical cancer; cervical cancer screening practices; HPV vaccine introduction; and other relevant immunisation indicators. The report is intended to strengthen the guidance for health policy implementation of primary and secondary cervical cancer prevention strategies in the country. Table 1: Key Statistics Population Women at risk for cervical cancer (Female aged >=15 years) 48.4 million Burden of cervical cancer and other HPV-related cancers Annual number of cervical cancer cases 7,869 Annual number of cervical cancer deaths 4,121 Crude incidence rates per 100,000 and year: Male Female Cervical cancer - 12.0 Anal cancer - - Vulvar cancer - - Vaginal cancer - - Penile cancer - - Oropharyngeal cancer 0.5 0.2 Burden of cervical HPV infection Prevalence (%) of HPV 16 and/or HPV 18 among women with: Normal cytology 5.1 Low-grade cervical lesions (LSIL/CIN-1) 15.3 High-grade cervical lesions (HSIL/CIN-2/CIN-3/CIS) 37.7 Cervical cancer 65.0 Other factors contributing to cervical cancer Smoking prevalence (%), women 7.3 [5.9-8.8] Total fertility rate (live births per women) 2.3 Oral contraceptive use (%) among women 4.7 HIV prevalence (%), adults (15-49 years) 0.2 [0.2-0.3] Sexual behaviour Percentage of 15-year-old who have had sexual intercourse (men/women) - / - Range of median age at first sexual intercourse (men/women) - / - Cervical screening practices and recommendations Cervical cancer screening coverage, 42.8% (All women aged >20 screened every 1y, ENSANUT 2012 Mexico (a)) % (age and screening in- terval, reference) Screening ages (years) 25-64 Screening interval (years) or Cytology every 3 years, after 2 consecutive annual negative tests frequency of screens HPV vaccine HPV vaccine introduction HPV vaccination programme National program Date of HPV vaccination routine immunization programme start 2012 Please see the specific sections for more information.

CONTENTS - iv - Contents Executive summary iii 1 Introduction 2 2 Demographic and socioeconomic factors 4 3 Burden of HPV related cancers 6 3.1 Cervical cancer.............................................. 6 3.1.1 Cervical cancer incidence in Mexico............................. 6 3.1.2 Cervical cancer incidence by histology in Mexico...................... 10 3.1.3 Cervical cancer incidence in Mexico across Central America............... 12 3.1.4 Cervical cancer mortality in Mexico............................. 14 3.1.5 Cervical cancer mortality in Mexico across Central America.............. 18 3.1.6 Cervical cancer incidence and mortality comparison, Premature deaths and disability in Mexico......................................... 20 3.2 Anogenital cancers other than the cervix.............................. 22 3.2.1 Anal cancer............................................ 22 3.2.2 Vulvar cancer........................................... 24 3.2.3 Vaginal cancer.......................................... 25 3.2.4 Penile cancer........................................... 26 3.3 Head and neck cancers......................................... 27 3.3.1 Oropharyngeal cancer...................................... 27 4 HPV related statistics 30 4.1 HPV burden in women with normal cervical cytology, cervical precancerous lesions or invasive cervical cancer......................................... 30 4.1.1 HPV prevalence in women with normal cervical cytology................ 31 4.1.2 HPV type distribution among women with normal cervical cytology, precancerous cervical lesions and cervical cancer.............................. 33 4.1.3 HPV type distribution among HIV+ women with normal cervical cytology...... 42 4.1.4 Terminology............................................ 43 4.2 HPV burden in anogenital cancers other than cervix....................... 44 4.2.1 Anal cancer and precancerous anal lesions......................... 44 4.2.2 Vulvar cancer and precancerous vulvar lesions....................... 46 4.2.3 Vaginal cancer and precancerous vaginal lesions..................... 48 4.2.4 Penile cancer and precancerous penile lesions....................... 50 4.3 HPV burden in men........................................... 52 4.4 HPV burden in the head and neck.................................. 54 4.4.1 Burden of oral HPV infection in healthy.................... 54 4.4.2 HPV burden in head and neck cancers............................ 54 5 Factors contributing to cervical cancer 56 6 Sexual and reproductive health behaviour indicators 58 7 HPV preventive strategies 59 7.1 Cervical cancer screening practices.................................. 59 7.2 HPV vaccination............................................. 64 8 Protective factors for cervical cancer 65

LIST OF CONTENTS - v - 9 Indicators related to immunisation practices other than HPV vaccines 67 9.1 Immunisation schedule......................................... 67 9.2 Immunisation coverage estimates................................... 67 10 Glossary 69

LIST OF FIGURES - vi - List of Figures 1 Mexico and Central America................................................... 2 2 Population pyramid of Mexico for 2017............................................. 4 3 Population trends in four selected age groups in Mexico.................................. 4 4 HPV-related cancer incidence in Mexico (estimates for 2012)............................... 6 5 Comparison of cervical cancer incidence to other cancers in women of all ages in Mexico (estimates for 2018).. 7 6 Comparison of age-specific cervical cancer to age-specific incidence of other cancers among women 15-44 years of age in Mexico (estimates for 2018).............................................. 8 7 Annual number of cases and age-specific incidence rates of cervical cancer in Mexico (estimates for 2018).... 9 8 Time trends in cervical cancer incidence in Mexico (cancer registry data)........................ 11 9 Age-standardised incidence rates of cervical cancer of Mexico (estimates for 2018).................. 12 10 Annual number of new cases of cervical cancer by age group in Mexico (estimates for 2018)............. 13 11 Comparison of cervical cancer mortality to other cancers in women of all ages in Mexico (estimates for 2018).. 15 12 Comparison of age-specific mortality rates of cervical cancer to other cancers among women 15-44 years of age in Mexico (estimates for 2018).................................................. 16 13 Annual number of deaths and age-specific mortality rates of cervical cancer in Mexico (estimates for 2018)... 17 14 Comparison of age-standardised cervical cancer mortality rates in Mexico and countries within the region (estimates for 2018)........................................................... 18 15 Annual deaths number of cervical cancer by age group in Mexico (estimates for 2018)................ 19 16 Comparison of age-specific cervical cancer incidence and mortality rates in Mexico (estimates for 2018)..... 20 17 Comparison of annual premature deaths and disability from cervical cancer in Mexico to other cancers among women (estimates for 2008)................................................... 21 18 Time trends in anal cancer incidence in Mexico (cancer registry data).......................... 23 19 Time trends in vulvar cancer incidence in Mexico (cancer registry data)......................... 24 20 Time trends in vaginal cancer incidence in Mexico (cancer registry data)........................ 25 21 Time trends in penile cancer incidence in Mexico (cancer registry data)......................... 26 22 Comparison of incidence and mortality rates of the oropharynx by age group and sex in Mexico (estimates for 2018). Includes ICD-10 codes: C09-10............................................. 28 23 Crude age-specific HPV prevalence (%) and 95% confidence interval in women with normal cervical cytology in Mexico................................................................ 31 24 HPV prevalence among women with normal cervical cytology in Mexico, by study................... 32 25 HPV 16 prevalence among women with normal cervical cytology in Mexico, by study................. 33 26 HPV 16 prevalence among women with low-grade cervical lesions in Mexico, by study................ 34 27 HPV 16 prevalence among women with high-grade cervical lesions in Mexico, by study............... 34 28 HPV 16 prevalence among women with invasive cervical cancer in Mexico, by study................. 34 29 Comparison of the ten most frequent HPV oncogenic types in Mexico among women with and without cervical lesions................................................................ 35 30 Comparison of the ten most frequent HPV oncogenic types in Mexico among women with invasive cervical cancer by histology............................................................. 37 31 Comparison of the ten most frequent HPV types in anal cancer cases in the Americas and the World....... 45 32 Comparison of the ten most frequent HPV types in AIN 2/3 cases in the Americas and the World......... 45 33 Comparison of the ten most frequent HPV types in cases of vulvar cancer in the Americas and the World.... 47 34 Comparison of the ten most frequent HPV types in VIN 2/3 cases in the Americas and the World......... 47 35 Comparison of the ten most frequent HPV types in cases of vaginal cancer in the Americas and the World.... 49 36 Comparison of the ten most frequent HPV types in VaIN 2/3 cases in the Americas and the World......... 49 37 Comparison of the ten most frequent HPV types in cases of penile cancer in the Americas and the World.... 51 38 Comparison of the ten most frequent HPV types in PeIN 2/3 cases in the Americas and the World......... 51 39 Estimated coverage of cervical cancer screening in Mexico, by age and study...................... 60 40 Reported HPV vaccination coverage in females by birth cohort in National HPV Immunization programme in Mexico................................................................ 64 41 Reported HPV vaccination coverage in females by birth cohort in National HPV Immunization programme in 125 targeted municipalities that started in 2008 (Mexico)................................. 65

LIST OF TABLES - 1 - List of Tables 1 Key Statistics............................................................ iii 2 Sociodemographic indicators in Mexico............................................. 5 3 Cervical cancer incidence in Mexico (estimates for 2018).................................. 7 4 Cervical cancer incidence in Mexico by cancer registry................................... 7 5 Age-standardised incidence rates of cervical cancer in Mexico by histological type and cancer registry...... 10 6 Cervical cancer mortality in Mexico (estimates for 2018).................................. 14 7 Premature deaths and disability from cervical cancer in Mexico, Central America and the rest of the world (estimates for 2008)........................................................ 20 8 Anal cancer incidence in Mexico by cancer registry and sex................................ 22 9 Vulvar cancer incidence in Mexico by cancer registry.................................... 24 10 Vaginal cancer incidence in Mexico by cancer registry.................................... 25 11 Penile cancer incidence in Mexico by cancer registry.................................... 26 12 Incidence and mortality of cancer of the oropharynx in Mexico, Central America and the rest of the world by sex (estimates for 2018). Includes ICD-10 codes: C09-10.................................... 27 13 Incidence of oropharyngeal cancer in Mexico by cancer registry and sex......................... 29 14 Prevalence of HPV16 and HPV18 by cytology in Mexico.................................. 33 15 Type-specific HPV prevalence in women with normal cervical cytology, precancerous cervical lesions and invasive cervical cancer in Mexico..................................................... 38 16 Type-specific HPV prevalence among invasive cervical cancer cases in Mexico by histology............. 40 17 Studies on HPV prevalence among HIV women with normal cytology in Mexico.................... 42 18 Studies on HPV prevalence among anal cancer cases in Mexico (male and female).................. 44 19 Studies on HPV prevalence among cases of AIN2/3 in Mexico............................... 44 20 Studies on HPV prevalence among vulvar cancer cases in Mexico............................. 46 21 Studies on HPV prevalence among VIN 2/3 cases in Mexico................................ 46 22 Studies on HPV prevalence among vaginal cancer cases in Mexico............................ 48 23 Studies on HPV prevalence among VaIN 2/3 cases in Mexico............................... 48 24 Studies on HPV prevalence among penile cancer cases in Mexico............................. 50 25 Studies on HPV prevalence among PeIN 2/3 cases in Mexico................................ 50 26 Studies on HPV prevalence among men in Mexico...................................... 52 27 Studies on HPV prevalence among men from special subgroups in Mexico....................... 53 28 Studies on oral HPV prevalence among healthy in Mexico................................. 54 29 Studies on HPV prevalence among cases of oral cavity cancer in Mexico......................... 54 30 Studies on HPV prevalence among cases of oropharyngeal cancer in Mexico...................... 55 31 Studies on HPV prevalence among cases of hypopharyngeal or laryngeal cancer in Mexico............. 55 32 Factors contributing to cervical carcinogenesis (cofactors) in Mexico........................... 56 33 Percentage of 15-year-olds who have had sexual intercourse in Mexico......................... 58 34 Marriage patterns in Mexico................................................... 58 35 Main characteristics of cervical cancer screening in Mexico................................ 59 36 Estimated coverage of cervical cancer screening in Mexico................................. 60 37 Estimated coverage of cervical cancer screening in Mexico, by region.......................... 61 38 National HPV Immunization programme in Mexico..................................... 64 39 Prevalence of male circumcision in Mexico.......................................... 65 40 Prevalence of condom use in Mexico.............................................. 66 41 General immunization schedule in Mexico........................................... 67 42 Immunization coverage estimates in Mexico......................................... 68 43 Glossary............................................................... 69

1 INTRODUCTION - 2-1 Introduction Figure 1: Mexico and Central America The HPV Information Centre aims to compile and centralise updated data and statistics on human papillomavirus (HPV) and related cancers. This report aims to summarise the data available to fully evaluate the burden of disease in Mexico and to facilitate stakeholders and relevant bodies of decision makers to formulate recommendations on cervical cancer prevention. Data include relevant cancer statistic estimates, epidemiological determinants of cervical cancer such as demographics, socioeconomic factors, risk factors, burden of HPV infection, screening and immunisation. The report is structured into the following sections: Section 2, Demographic and socioeconomic factors. This section summarises the socio-demographic profile of country. For analytical purposes, Mexico is classified in the geographical region of Central America (Figure 1, lighter blue), which is composed of the following countries: Belize, Costa

1 INTRODUCTION - 3 - Rica, Guatemala, Honduras, Mexico, Nicaragua, Panama, El Salvador. Throughout the report, Mexico estimates will be complemented with corresponding regional estimates. Section 3, Burden of HPV related cancers. This section describes the current burden of invasive cervical cancer and other HPV-related cancers in Mexico and the Central America region with estimates of prevalence, incidence, and mortality rates. Section 4, HPV related statistics. This section reports on prevalence of HPV and HPV type-specific distribution in Mexico, in women with normal cytology, precancerous lesions and invasive cervical cancer. In addition, the burden of HPV in other anogenital cancers (anus, vulva, vagina, and penis) and men are presented. Section 5, Factors contributing to cervical cancer. This section describes factors that can modify the natural history of HPV and cervical carcinogenesis such as smoking, parity, oral contraceptive use, and co-infection with HIV. Section 6, Sexual and reproductive health behaviour indicators. This section presents sexual and reproductive behaviour indicators that may be used as proxy measures of risk for HPV infection and anogenital cancers. Section 7, HPV preventive strategies. This section presents preventive strategies that include basic characteristics and performance of cervical cancer screening status, status of HPV vaccine licensure introduction, and recommendations in national immunisation programmes. Section 8, Protective factors for cervical cancer. This section presents the prevalence of male circumcision and condom use. Section 9, Indicators related to immunisation practices other than HPV vaccines. This section presents data on immunisation coverage and practices for selected vaccines. This information will be relevant for assessing the country s capacity to introduce and implement the new vaccines. The data are periodically updated and posted on the WHO immunisation surveillance, assessment and monitoring website at http://www.who.int/immunization_monitoring/en/.

2 DEMOGRAPHIC AND SOCIOECONOMIC FACTORS - 4-2 Demographic and socioeconomic factors Figure 2: Population pyramid of Mexico for 2017 Males Females 80+ 75 79 70 74 65 69 60 64 55 59 50 54 45 49 40 44 35 39 30 34 25 29 20 24 15 19 10 14 5 9 Under 5 836,287 1,210,915 729,388 837,343 1,070,898 1,147,808 1,495,886 1,590,366 2,035,390 2,231,674 2,472,682 2,727,473 3,099,868 3,315,107 3,849,841 4,000,375 4,333,748 4,549,908 4,643,750 4,817,840 5,018,650 5,032,960 5,481,524 5,347,577 5,871,922 5,711,347 6,039,789 5,858,041 5,970,773 5,739,541 5,908,822 5,647,521 5,920,467 5,677,334 Data accessed on 27 Mar 2017. Please refer to original source for methods of estimation. Year of estimate: 2017; United Nations, Department of Economic and Social Affairs, Population Division (2015). World Population Prospects: The 2015 Revision, DVD Edition. Available at: https://esa.un.org/ unpd/wpp/download/standard/population/. [Accessed on March 21, 2017]. Number of women (in millions) 12 10 8 6 4 2 0 Figure 3: Population trends in four selected age groups in Mexico Projections Women 15 24 yrs Girls 10 14 yrs 1950 1960 1970 1980 1990 2000 2010 2020 2030 2040 2050 2060 2070 2080 2090 2100 Number of women (in millions) Projections 101 All Women 51 Women 25 64 yrs 1 1950 1960 1970 1980 1990 2000 2010 2020 2030 2040 2050 2060 2070 2080 2090 2100 Female trends in Mexico Number of women by year and age group Data accessed on 27 Mar 2017. Please refer to original source for methods of estimation. Year of estimate: 2017; United Nations, Department of Economic and Social Affairs, Population Division (2015). World Population Prospects: The 2015 Revision, DVD Edition. Available at: https://esa.un.org/ unpd/wpp/download/standard/population/. [Accessed on March 21, 2017].

2 DEMOGRAPHIC AND SOCIOECONOMIC FACTORS - 5 - Table 2: Sociodemographic indicators in Mexico Indicator Male Female Total Population in thousands 1,± 64,779.7 65,443.1 130,222.8 Population growth rate (%) 1, - - 1.4 Median age of the (in years) 1, - - 27.4 Population living in urban areas (%) 2, - - 79.2 Crude birth rate (births per 1,000) 1, - - 19.3 Crude death rate (deaths per 1,000) 1, - - 4.8 Life expectancy at birth (in years) 3,a,b, 73.9 79.5 76.7 Adult mortality rate (probability of dying between 15 and 60 years old per 161 82 122 1,000) 4, Maternal mortality ratio (per 100,000 live births) 3,c, - - 38 Under age five mortality rate (per 1,000 live births) 3,d, - - 13.2 Density of physicians (per 1,000 ) 5,e, - - 2.071 Gross national income per capita (PPP current international $) 6,f, - - 16860 Adult literacy rate (%) (aged 15 and older) 7,g, 95.6 93.5 94.5 Youth literacy rate (%) (aged 15-24 years) 7,g, 98.7 98.8 98.7 Net primary school enrollment ratio 7, 94.7 95.5 95.1 Net secondary school enrollment ratio 7, 66.1 68.8 67.4 Data accessed on 27 Mar 2017. Please refer to original source for methods of estimation. a World Population Prospects, the 2015 revision (WPP2015). New York (NY): United Nations DESA, Population Division. b WHO annual life tables for 1985 2015 based on the WPP2015, on the data held in the WHO Mortality Database and on HIV mortality estimates prepared by UNAIDS. WHO Member States with a of less than 90 000 in 2015 were not included in the analysis. c WHO, UNICEF, UNFPA, World Bank Group and the United Nations Population Division. Trends in maternal mortality: 1990 to 2015. Estimates by WHO, UNICEF, UNFPA, World Bank Group and the United Nations Population Division. Geneva: World Health Organization; 2015 (http://www.who.int/reproductivehealth/publications/monitoring/ maternal-mortality-2015/en/, accessed 25 March 2016). WHO Member States with a of less than 100 000 in 2015 were not included in the analysis. d Levels & Trends in Child Mortality. Report 2015. Estimates Developed by the UN Inter-agency Group for Child Mortality Estimation. New York (NY), Geneva and Washington (DC): United Nations Children s Fund, World Health Organization, World Bank and United Nations; 2015 (http://www.unicef.org/publications/files/child_mortality_report_2015_ Web_9_Sept_15.pdf, accessed 26 March 2016). e Number of medical doctors (physicians), including generalist and specialist medical practitioners, per 1 000. f GNI per capita based on purchasing power parity (PPP). PPP GNI is gross national income (GNI) converted to international dollars using purchasing power parity rates. An international dollar has the same purchasing power over GNI as a U.S. dollar has in the United States. GNI is the sum of value added by all resident producers plus any product taxes (less subsidies) not included in the valuation of output plus net receipts of primary income (compensation of employees and property income) from abroad. Data are in current international dollars based on the 2011 ICP round. g UIS Estimation Year of estimate: ± 2017; 2010-2015; 2015; 2013; 2014; 2012; 1 United Nations, Department of Economic and Social Affairs, Population Division (2015). World Population Prospects: The 2015 Revision, DVD Edition. Available at: https://esa.un. org/unpd/wpp/download/standard/population/. [Accessed on March 21, 2017]. 2 United Nations, Department of Economic and Social Affairs, Population Division (2014). World Urbanization Prospects: The 2014 Revision, CD-ROM Edition. Available at: https: //esa.un.org/unpd/wup/cd-rom/. [Accessed on March 21, 2017]. 3 World Health Statistics 2016. Geneva, World Health Organization, 2016. Available at: http://who.int/entity/gho/publications/world_health_statistics/2016/en/index. html. [Accessed on March 21, 2017]. 4 World Health Organization. Global Health Observatory data repository. Available at: http://apps.who.int/gho/data/view.main.1360?lang=en. [Accessed on March 21, 2017]. 5 The 2016 update, Global Health Workforce Statistics, World Health Organization, Geneva (http://www.who.int/hrh/statistics/hwfstats/). [Accessed on March 21, 2017]. 6 World Bank, World Development Indicators Database. Washington, DC. International Comparison Program database. Available at: http://databank.worldbank.org/data/reports. aspx?source=world-development-indicators#. [Accessed on March 21, 2017]. 7 UNESCO Institute for Statistics Data Centre [online database]. Montreal, UNESCO Institute for Statistics. Available at: http://stats.uis.unesco.org [Accessed on March 21, 2017].

3 BURDEN OF HPV RELATED CANCERS - 6-3 Burden of HPV related cancers HPV is the cause of almost all cervical cancer cases and is responsible for an important fraction of other anogenital and head and neck cancer. Here, we present the most recent estimations on the burden of HPV-associated cancer. Figure 4: HPV-related cancer incidence in Mexico (estimates for 2012) Cervix uteri 23.3 Other anogenital (a) 0.9 Head and neck (b) 0.1 0 10 20 Age standardised incidence rate per 100,0000 women World Standard Data accessed on 08 May 2017. a Other anogenital cancer cases (vulvar, vaginal, anal, and penile). b Head and neck cancer cases (oropharynx, oral cavity and larynx). ASR: Age-standardized rate, rates per 100,000 per year. Please refer to original source for methods. GLOBOCAN quality index for availability of incidence data: Regional data (rates). GLOBOCAN quality index of methods for calculating incidence: Methods to estimate the sex- and age-specific incidence rates of cancer for a specific country: Estimated from national mortality estimates using modelled survival de Martel C, Plummer M, Vignat J, Franceschi S. Worldwide burden of cancer attributable to HPV by site, country and HPV type. Int J Cancer. 2017 3.1 Cervical cancer Cancer of the cervix uteri is the 3rd most common cancer among women worldwide, with an estimated 569,847 new cases and 311,365 deaths in 2018 (GLOBOCAN). The majority of cases are squamous cell carcinoma followed by adenocarcinomas. (Vaccine 2006, Vol. 24, Suppl 3; Vaccine 2008, Vol. 26, Suppl 10; Vaccine 2012, Vol. 30, Suppl 5; IARC Monographs 2007, Vol. 90) This section describes the current burden of invasive cervical cancer in Mexico and in comparison to geographic region, including estimates of the annual number of new cases, deaths, incidence, and mortality rates. 3.1.1 Cervical cancer incidence in Mexico KEY STATS. About 7,869 new cervical cancer cases are diagnosed annually in Mexico (estimates for 2018). Cervical cancer ranks* as the 3 rd leading cause of female cancer in Mexico. Cervical cancer is the 3 th most common female cancer in women aged 15 to 44 years in Mexico.

3 BURDEN OF HPV RELATED CANCERS - 7 - * Ranking of cervical cancer incidence to other cancers among all women according to highest incidence rates (ranking 1st) excluding non-melanoma skin cancer. Ranking is based on crude incidence rates (actual number of cervical cancer cases). Ranking using age-standardized rate (ASR) may differ. Table 3: Cervical cancer incidence in Mexico (estimates for 2018) Indicator Mexico Central America World Annual number of new cancer cases 7,869 12,406 569,847 Crude incidence rate a 12.0 13.7 15.1 Age-standardized incidence rate a 11.0 13.0 13.1 Cumulative risk (%) at 75 years old b 1 1 1 Data accessed on 05 Oct 2018. For more detailed methods of estimation please refer to http://gco.iarc.fr/today/data-sources-methods a Rates per 100,000 women per year. b Cumulative risk (incidence) is the probability or risk of individuals getting from the disease during ages 0-74 years. For cancer, it is expressed as the % of new born children who would be expected to develop from a particular cancer before the age of 75 if they had the rates of cancer observed in the period in the absence of competing causes. Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, Bray F (2018). Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. Available from: https://gco.iarc.fr/today, accessed [05 October 2018]. Table 4: Cervical cancer incidence in Mexico by cancer registry Cancer registry Period N cases a Crude rate b ASR b No Data Available - - - - Data accessed on 05 Oct 2018. ASR: Age-standardized rate, Standardized rates have been estimated using the direct method and the World as the reference; Please refer to original source (available at http://ci5.iarc.fr/ci5-xi/default.aspx) a Accumulated number of cases during the period in the covered by the corresponding registry. b Rates per 100,000 women per year. Figure 5: Comparison of cervical cancer incidence to other cancers in women of all ages in Mexico (estimates for 2018) Breast Thyroid Cervix uteri Corpus uteri Colon Ovary Liver Stomach Lung Leukaemia Pancreas Non Hodgkin lymphoma Gallbladder Kidney Rectum Melanoma of skin Brain, nervous system Lip, oral cavity Hodgkin lymphoma Multiple myeloma Bladder Vulva Salivary glands Oesophagus Vagina Larynx Anus Mesothelioma Nasopharynx Oropharynx Kaposi sarcoma Hypopharynx 12.0 15.5 41.6 11.1 3.0 3.5 4.0 4.4 5.0 5.5 5.8 7.2 7.8 2.9 2.7 1.7 2.4 2.6 1.4 1.1 1.0 0.6 0.5 0.4 0.4 0.4 0.3 0.2 0.2 0.2 0.1 0.0 0 10 20 30 40 50 60 Annual crude incidence rate per 100,000 Mexico: Female (All ages)

3 BURDEN OF HPV RELATED CANCERS - 8 - Data accessed on 07 Oct 2018. Non-melanoma skin cancer is not included. Rates per 100,000 women per year. Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, Bray F (2018). Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. Available from: https://gco.iarc.fr/today, accessed [05 October 2018]. Figure 6: Comparison of age-specific cervical cancer to age-specific incidence of other cancers among women 15-44 years of age in Mexico (estimates for 2018) Breast Thyroid Cervix uteri Corpus uteri Ovary Leukaemia Colon Non Hodgkin lymphoma Stomach Hodgkin lymphoma Brain, nervous system Melanoma of skin Rectum Kidney Lung Lip, oral cavity Liver Gallbladder Salivary glands Pancreas Multiple myeloma Vulva Bladder Nasopharynx Larynx Vagina Oesophagus Anus Oropharynx Kaposi sarcoma Mesothelioma Hypopharynx 4.7 4.6 1.5 1.82.5 1.1 1.3 1.4 1.0 0.5 0.8 0.9 0.5 0.4 0.3 0.3 0.3 0.2 0.2 0.1 0.1 0.1 0.1 0.1 0.0 0.0 0.0 0.0 0.0 9.2 14.6 22.5 0 5 10 15 20 25 30 Annual crude incidence rate per 100,000 Mexico: Female (15 44 years) Data accessed on 07 Oct 2018. Non-melanoma skin cancer is not included. Rates per 100,000 women per year. Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, Bray F (2018). Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. Available from: https://gco.iarc.fr/today, accessed [05 October 2018].

3 BURDEN OF HPV RELATED CANCERS - 9 - Figure 7: Annual number of cases and age-specific incidence rates of cervical cancer in Mexico (estimates for 2018) 40 30 20 10 0 15 19 Age specific rates of cervical cancer 20 24 25 29 30 34 35 39 40 44 45 49 50 54 55 59 60 64 65 69 Annual number of new cases of cervical cancer 70 74 75+ 5000 4500 4000 3500 3000 2500 2000 1500 1000 500 0 1944* 4114 60 64 yrs: 665 cases 55 59 yrs: 739 cases 50 54 yrs: 814 cases 45 49 yrs: 955 cases 40 44 yrs: 941 cases 1810 15 39 40 64 65+ Age group (years) *15-19 yrs: 8 cases. 20-24 yrs: 175 cases. 25-29 yrs: 405 cases. 30-34 yrs: 591 cases. 35-39 yrs: 765 cases. Data accessed on 05 Oct 2018. Rates per 100,000 women per year. Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, Bray F (2018). Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. Available from: https://gco.iarc.fr/today, accessed [05 October 2018].

3 BURDEN OF HPV RELATED CANCERS - 10-3.1.2 Cervical cancer incidence by histology in Mexico Table 5: Age-standardised incidence rates of cervical cancer in Mexico by histological type and cancer registry Carcinoma Cancer registry Period Squamous Adeno Other Unspec. No data available - - - - - Data accessed on 05 Oct 2018. Adeno: adenocarcinoma; Other: Other carcinoma; Squamous: Squamous cell carcinoma; Unspec: Unspecified carcinoma; Rates per 100,000 women per year. Standarized rates have been estimated using the direct method and the World as the references.

3 BURDEN OF HPV RELATED CANCERS - 11 - Figure 8: Time trends in cervical cancer incidence in Mexico (cancer registry data) Cervix uteri Annual crude incidence rate (per 100,000) No data available All ages (2) 15 44 yrs (2) 45 74 yrs (2) 1975 1980 1985 1990 1995 Cervix uteri: Squamous cell carcinoma Annual crude incidence rate (per 100,000) No data available All ages (2) 15 44 yrs (2) 45 74 yrs (2) 1975 1980 1985 1990 1995 Cervix uteri: Adenocarcinoma Annual crude incidence rate (per 100,000) No data available All ages (2) 15 44 yrs (2) 45 74 yrs (2) 1975 1980 1985 1990 1995 Data accessed on 27 Apr 2015. a Estimated annual percentage change based on the trend variable from the net drift for the most recent two 5-year periods. 1 Vaccarella S, Lortet-Tieulent J, Plummer M, Franceschi S, Bray F. Worldwide trends in cervical cancer incidence: Impact of screening against changes in disease risk factors. eur J Cancer 2013;49:3262-73. 2 Ferlay J, Bray F, Steliarova-Foucher E and Forman D. Cancer Incidence in Five Continents, CI5plus: IARC CancerBase No. 9 [Internet]. Lyon, France: International Agency for Research on Cancer; 2014. Available from: http://ci5.iarc.fr

3 BURDEN OF HPV RELATED CANCERS - 12-3.1.3 Cervical cancer incidence in Mexico across Central America Figure 9: Age-standardised incidence rates of cervical cancer of Mexico (estimates for 2018) Belize 28 Nicaragua 21.2 Guatemala 21.1 Honduras 19.6 El Salvador 18.5 Panama 18.4 Costa Rica 11.2 Mexico 11 0 5 10 15 20 25 30 Cervical cancer: Age standardised incidence rate per 100,000 women World Standard. Female (All ages) Data accessed on 05 Oct 2018. Rates per 100,000 women per year. Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, Bray F (2018). Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. Available from: https://gco.iarc.fr/today, accessed [05 October 2018].

3 BURDEN OF HPV RELATED CANCERS - 13 - Figure 10: Annual number of new cases of cervical cancer by age group in Mexico (estimates for 2018) Mexico Central America 2000 Annual number of new cases of cervical cancer 1750 1500 1250 1000 750 500 250 266 175 652 405 960 591 1242 765 1471 941 1476 955 1289 814 1153 739 1018 665 819 539 621 401 1427 870 0 * 15 19 20 24 25 29 30 34 35 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 >=75 Age group (years) *8 cases for Mexico and 11 cases for Central America in the 15-19 age group. Data accessed on 05 Oct 2018. Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, Bray F (2018). Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. Available from: https://gco.iarc.fr/today, accessed [05 October 2018].

3 BURDEN OF HPV RELATED CANCERS - 14-3.1.4 Cervical cancer mortality in Mexico KEY STATS. About 4,121 cervical cancer deaths occur annually in Mexico (estimates for 2018). Cervical cancer ranks* as the 2 nd leading cause of female cancer deaths in Mexico. Cervical cancer is the 2 nd leading cause of cancer deaths in women aged 15 to 44 years in Mexico. * Ranking of cervical cancer incidence to other cancers among all women according to highest incidence rates (ranking 1st) excluding non-melanoma skin cancer. Ranking is based on crude incidence rates (actual number of cervical cancer cases). Ranking using age-standardized rate (ASR) may differ. Table 6: Cervical cancer mortality in Mexico (estimates for 2018) Indicator Mexico Central America World Annual number of deaths 4,121 6,619 311,365 Crude mortality rate a 6.3 7.3 8.2 Age-standardized mortality rate a 5.8 7.0 6.9 Cumulative risk (%) at 75 years old b 0.6 0.8 0.8 Data accessed on 05 Oct 2018. For more detailed methods of estimation please refer to http://gco.iarc.fr/today/data-sources-methods a Rates per 100,000 women per year. b Cumulative risk (mortality) is the probability or risk of individuals dying from the disease during ages 0-74 years. For cancer, it is expressed as the % of new born children who would be expected to die from a particular cancer before the age of 75 if they had the rates of cancer observed in the period in the absence of competing causes. Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, Bray F (2018). Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. Available from: https://gco.iarc.fr/today, accessed [05 October 2018].

3 BURDEN OF HPV RELATED CANCERS - 15 - Figure 11: Comparison of cervical cancer mortality to other cancers in women of all ages in Mexico (estimates for 2018) Breast Cervix uteri Liver Stomach Ovary Colon Lung Pancreas Leukaemia Gallbladder Brain, nervous system Non Hodgkin lymphoma Corpus uteri Kidney Multiple myeloma Thyroid Rectum Melanoma of skin Lip, oral cavity Bladder Oesophagus Hodgkin lymphoma Vulva Larynx Mesothelioma Salivary glands Vagina Oropharynx Nasopharynx Anus Kaposi sarcoma Hypopharynx 2.0 3.13.6 1.9 1.8 0.9 1.6 1.7 0.5 0.9 0.9 0.5 0.5 0.4 0.3 0.2 0.2 0.2 0.1 0.1 0.1 0.1 0.1 0.0 0.0 4.3 5.36.3 4.2 4.2 4.0 10.5 0 5 10 15 20 25 30 Annual crude mortality rate per 100,000 Mexico: Female (All ages) Data accessed on 07 Oct 2018. Non-melanoma skin cancer not included. a Rates per 100,000 women per year. Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, Bray F (2018). Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. Available from: https://gco.iarc.fr/today, accessed [05 October 2018].

3 BURDEN OF HPV RELATED CANCERS - 16 - Figure 12: Comparison of age-specific mortality rates of cervical cancer to other cancers among women 15-44 years of age in Mexico (estimates for 2018) Breast Cervix uteri Leukaemia Ovary Stomach Colon Brain, nervous system Non Hodgkin lymphoma Lung Liver Pancreas Corpus uteri Rectum Kidney Hodgkin lymphoma Melanoma of skin Gallbladder Thyroid Lip, oral cavity Multiple myeloma Nasopharynx Bladder Salivary glands Mesothelioma Larynx Kaposi sarcoma Vulva Oropharynx Vagina Oesophagus Anus Hypopharynx 0.2 0.3 0.4 0.4 0.50.7 0.2 0.1 0.2 0.2 0.1 0.1 0.0 0.1 0.1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 1.4 0.9 0.7 1.9 2.7 3.4 0 5 10 Annual crude mortality rate per 100,000 Mexico: Female (15 44 years) Data accessed on 07 Oct 2018. Non-melanoma skin cancer not included. a Rates per 100,000 women per year. Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, Bray F (2018). Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. Available from: https://gco.iarc.fr/today, accessed [05 October 2018].

3 BURDEN OF HPV RELATED CANCERS - 17 - Figure 13: Annual number of deaths and age-specific mortality rates of cervical cancer in Mexico (estimates for 2018) 40 30 20 10 0 15 19 20 24 25 29 30 34 35 39 40 44 45 49 50 54 55 59 60 64 Age specific rates of cervical cancer Annual number of deaths of cervical cancer 65 69 70 74 75+ 2500 2000 1500 1000 500 0 485* 2124 60 64 yrs: 436 cases 55 59 yrs: 440 cases 50 54 yrs: 440 cases 45 49 yrs: 445 cases 40 44 yrs: 363 cases 1512 15 39 40 64 65+ Age group (years) * 15-19 yrs: 2 cases. 20-24 yrs: 13 cases. 25-29 yrs: 71 cases. 30-34 yrs: 153 cases. 35-39 yrs: 246 cases. Data accessed on 05 Oct 2018. Rates per 100,000 women per year. Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, Bray F (2018). Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. Available from: https://gco.iarc.fr/today, accessed [05 October 2018].

3 BURDEN OF HPV RELATED CANCERS - 18-3.1.5 Cervical cancer mortality in Mexico across Central America Figure 14: Comparison of age-standardised cervical cancer mortality rates in Mexico and countries within the region (estimates for 2018) Belize 16.2 Nicaragua 13.3 Honduras 12.5 Guatemala 11.7 El Salvador 9.4 Panama 8.8 Mexico 5.8 Costa Rica 5.6 0 5 10 15 20 Cervical cancer: Age standardised mortality rate per 100,000 women World Standard. Female (All ages) Data accessed on 05 Oct 2018. Rates per 100,000 women per year. Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, Bray F (2018). Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. Available from: https://gco.iarc.fr/today, accessed [05 October 2018].

3 BURDEN OF HPV RELATED CANCERS - 19 - Figure 15: Annual deaths number of cervical cancer by age group in Mexico (estimates for 2018) Mexico Central America 1750 Annual number of new cases of cervical cancer 1500 1250 1000 750 500 250 0 1251 771 707 714 708 691 625 590 516 445 417 440 440 436 406 363 335 265 246 153 * * * 15 19 20 24 25 29 30 34 35 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 >=75 Age group (years) *2 cases for Mexico and 2 cases for Central America in the 15-19 age group. 13 cases for Mexico and 18 cases for Central America in the 20-24 age group. 71 cases for Mexico and 115 cases for Central America in the 25-29 age group. Data accessed on 05 Oct 2018. Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, Bray F (2018). Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. Available from: https://gco.iarc.fr/today, accessed [05 October 2018].

3 BURDEN OF HPV RELATED CANCERS - 20-3.1.6 Cervical cancer incidence and mortality comparison, Premature deaths and disability in Mexico Figure 16: Comparison of age-specific cervical cancer incidence and mortality rates in Mexico (estimates for 2018) Age specific rates of cervical cancer 40 30 20 10 Incidence Mortality 0 15 19 20 24 25 29 30 34 35 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 >=75 Age group (years) Data accessed on 05 Oct 2018. Rates per 100,000 women per year. Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, Bray F (2018). Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. Available from: https://gco.iarc.fr/today, accessed [05 October 2018]. Table 7: Premature deaths and disability from cervical cancer in Mexico, Central America and the rest of the world (estimates for 2008) Mexico Central America World Indicator Number ASR (W) Number ASR (W) Number ASR (W) Estimated disability-adjusted life 167,755 316 254,768 372 8,738,004 293 years (DALYs) Years of life lost (YLLs) 142,952 274 217,670 324 7,788,282 264 Years lived with disability (YLDs) 24,803 42 37,099 48 949,722 28 Data accessed on 04 Nov 2013. Soerjomataram I, Lortet-Tieulent J, Parkin DM, Ferlay J, Mathers C, Forman D, Bray F. Global burden of cancer in 2008: a systematic analysis of disability-adjusted life-years in 12 world regions. Lancet. 2012 Nov 24;380(9856):1840-50.

3 BURDEN OF HPV RELATED CANCERS - 21 - Figure 17: Comparison of annual premature deaths and disability from cervical cancer in Mexico to other cancers among women (estimates for 2008) Breast ca. Cervix uteri ca. Leukaemia Stomach ca. Liver ca. Lung ca. Ovarian ca. Colorectal ca. Pancreatic ca. Ca. of the brain and CNS Gallbladder Non Hodgkin lymphoma Corpus uteri ca. Kidney ca. Multiple myeloma Thyroid ca. Ca. of the lip and oral cavity Hodgkin lymphoma Melanoma of skin Oesophageal ca. Bladder ca. Laryngeal ca. Other pharynx ca. Nasopharyngeal ca. Kaposi sarcoma 68,397 62,916 54,367 54,334 46,292 39,323 34,369 33,640 29,155 26,433 18,158 9,302 8,355 7,574 6,945 5,869 5,813 5,535 3,119 2,269 740 0 93,804 167,755 186,906 YLLs YLDs 0 41200 82400 123600 164800 206000 Estimated disability adjusted life years (DALYs). Data accessed on 04 Nov 2013. CNS: Central Nervous System; YLDs: years lived with disability; YLLs: Years of life lost; Soerjomataram I, Lortet-Tieulent J, Parkin DM, Ferlay J, Mathers C, Forman D, Bray F. Global burden of cancer in 2008: a systematic analysis of disability-adjusted life-years in 12 world regions. Lancet. 2012 Nov 24;380(9856):1840-50.

3 BURDEN OF HPV RELATED CANCERS - 22-3.2 Anogenital cancers other than the cervix Data on HPV role in anogenital cancers other than cervix are limited, but there is an increasing body of evidence strongly linking HPV DNA with cancers of anus, vulva, vagina, and penis. Although these cancers are much less frequent compared to cervical cancer, their association with HPV make them potentially preventable and subject to similar preventative strategies as those for cervical cancer. (Vaccine 2006, Vol. 24, Suppl 3; Vaccine 2008, Vol. 26, Suppl 10; Vaccine 2012, Vol. 30, Suppl 5; IARC Monographs 2007, Vol. 90). 3.2.1 Anal cancer Anal cancer is rare in the general with an average worldwide incidence of 1 per 100,000, but is reported to be increasing in more developed regions. Globally, there are an estimated 27,000 new cases every year (de Martel C et al. Lancet Oncol 2012;13(6):607-15). Women have higher incidences of anal cancer than men. Incidence is particularly high among s of men who have sex with men (MSM), women with history of cervical or vulvar cancer, and immunosuppressed s, including those who are HIV-infected and patients with a history of organ transplantation. These cancers are predominantly squamous cell carcinoma, adenocarcinomas, or basaloid and cloacogenic carcinomas. Table 8: Anal cancer incidence in Mexico by cancer registry and sex MALE FEMALE Cancer registry Period N cases a Crude rate b ASR b N cases a Crude rate c ASR c No Data Available - - - - - - - Data accessed on 05 Oct 2018. ASR: Age-standardized rate, Standardized rates have been estimated using the direct method and the World as the reference; Please refer to original source (available at http://ci5.iarc.fr/ci5-xi/default.aspx) a Accumulated number of cases during the period in the covered by the corresponding registry. b Rates per 100,000 men per year. c Rates per 100,000 women per year.

3 BURDEN OF HPV RELATED CANCERS - 23 - Figure 18: Time trends in anal cancer incidence in Mexico (cancer registry data) Anal cancer in men Annual crude incidence rate (per 100,000) No data available All ages 15 44 yrs 45 74 yrs 1975 1980 1985 1990 1995 Anal cancer in women Annual crude incidence rate (per 100,000) No data available All ages 15 44 yrs 45 74 yrs 1975 1980 1985 1990 1995 Year Data accessed on 27 Apr 2015. Ferlay J, Bray F, Steliarova-Foucher E and Forman D. Cancer Incidence in Five Continents, CI5plus: IARC CancerBase No. 9 [Internet]. Lyon, France: International Agency for Research on Cancer; 2014. Available from: http://ci5.iarc.fr

3 BURDEN OF HPV RELATED CANCERS - 24-3.2.2 Vulvar cancer Cancer of the vulva is rare among women worldwide, with an estimated 27,000 new cases in 2008, representing 4% of all gynaecologic cancers (de Martel C et al. Lancet Oncol 2012;13(6):607-15). Worldwide, about 60% of all vulvar cancer cases occur in more developed countries. Vulvar cancer has two distinct histological patterns with two different risk factor profiles: (1) basaloid/warty types (2) keratinising types. Basaloid/warty lesions are more common in young women, are very often associated with HPV DNA detection (75-100%), and have a similar risk factor profile as cervical cancer. Keratinising vulvar carcinomas represent the majority of the vulvar lesions (>60%), they occur more often in older women and are more rarely associated with HPV (IARC Monograph Vol 100B). Table 9: Vulvar cancer incidence in Mexico by cancer registry Cancer registry Period N cases a Crude rate b ASR b No Data Available - - - - Data accessed on 05 Oct 2018. ASR: Age-standardized rate, Standardized rates have been estimated using the direct method and the World as the reference; Please refer to original source (available at http://ci5.iarc.fr/ci5-xi/default.aspx) a Accumulated number of cases during the period in the covered by the corresponding registry. b Rates per 100,000 women per year. Figure 19: Time trends in vulvar cancer incidence in Mexico (cancer registry data) Annual crude incidence rate (per 100,000) No data available All ages 15 44 yrs 45 74 yrs 1975 1980 1985 1990 1995 Year Data accessed on 27 Apr 2015. Ferlay J, Bray F, Steliarova-Foucher E and Forman D. Cancer Incidence in Five Continents, CI5plus: IARC CancerBase No. 9 [Internet]. Lyon, France: International Agency for Research on Cancer; 2014. Available from: http://ci5.iarc.fr